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Purpose. Fast kV-switching (FKS) and dual-layer flat-panel detector (DL-FPD) technologies have been actively studied as promising dual-energy spectral imaging solutions for FPD-based cone-beam computed tomography (CT). However, cone-beam CT (CBCT) spectral imaging is known to face challenges in obtaining accurate and robust material discrimination performance. That is because the energy separation by either FKS or DL-FPD, alone, is still limited, along with apparently unpaired signal levels in the effective low- and high-energy projections in real applications, not to mention the x-ray scatter in cone-beam scan which will make the material decomposition almost impossible if no correction is applied. To further improve CBCT spectral imaging capability, this work aims to promote a source-detector joint multi-energy spectral imaging solution which takes advantages of both FKS and DL-FPD, and to conduct a feasibility study on the first tabletop CBCT system with the joint spectral imaging capability developed. Methods. For CBCT, development of multi-energy spectral imaging can be jointly realized by using an x-ray source with a generator whose kilo-voltages can alternate in tens of Hertz (i.e. FKS), and a DL-FPD whose top- and bottom-layer projections corresponds to different effective energy levels. Thanks to the complimentary characteristics inherent in FKS and DL-FPD, the overall energy separation will be significantly better when compared with FKS or DL-FPD alone, and the x-ray photon detection efficiency will be also improved when compared with FKS alone. In this work, a noise performance analysis using the Cramér–Rao lower bound (CRLB) method is conducted. The CRLB for basis material after a projection-domain material decomposition is derived, followed by a set of numerical calculations of CRLBs, for the FKS, the DL-FPD and the joint solution, respectively. To compensate for the slightly angular mismatch between low- and high- projections in FKS, a dual-domain projection completion scheme is implemented. Afterwards material decomposition from the complete projection data is carried out by using the maximum-likelihood method, followed by reconstruction of basis material and virtual monochromatic images (VMI). In this work, the first FKS and DL-FPD jointly enabled multi-energy tabletop CBCT system, to the best of our knowledge, has been developed in our laboratory. To evaluate its spectral imaging performance, a set of physics experiments are conducted, where the multi-energy and head phantoms are scanned using the 80/105/130 kVp switching pairs and projection data are collected using a prototype DL-FPD, whose both top and bottom layer of panels are composed of 550 μ m of cesium iodine (CsI) scintillators with no intermediate metal filter in-between. Results. The numerical simulations show that the joint spectral imaging solution can lead to a significant improvement in energy separation and lower noise levels in most of material decomposition cases. The physics experiments confirmed the feasibility and superiority of the joint spectral imaging, whose CNRs in the selected regions of interest of the multi-energy phantom were boosted by an average improvement of 21.9%, 20.4% for water basis images and 32.8%, 62.8% for iodine images when compared with that of the FKS and DL-FPD, respectively. For the head phantom case, the joint spectral imaging can effectively reduce the streaking artifacts as well, and the standard deviation in the selected regions of interest are reduced by an average decrement of 19.5% and 8.1% for VMI when compared with that of the FKS and DL-FPD, respectively. Conclusions. A feasibility study of the joint spectral imaging solution for CBCT by utilizing both the FKS and DL-FPD was conducted, with the first tabletop CBCT system having such a capability being developed, which exhibits improved CNR and is more effective in avoiding streaking artifacts as expected. [ABSTRACT FROM AUTHOR]